Chlorofluorophenoxyalkanols and esters thereof



3,188,338 Patented June 8, 19 65 3,138,338 cinonoFLUonormNoxYALKANoLsAND Esrnas THEREOF Everett E. Gilbert, Morris Township, Morris County,NJ

and Christ N. Yiannois, Los Angeles, Calif., assignors to AlliedChemical Corporation, New York, N. a corporation of New York No Drawing.Filed July 16, 1958, Ser. No. 748,829 6 Claims. (Cl. 260-458) Thisinvention relates to 2(2-chloro-4-fluorophenoxy) ethanol-1, 4(2-chloro-4fluorophenoxy) butanol-l, and the esters thereof. The invention lies inthe discovery of these compounds as new products, and the discovery ofherbicidal properties of the same,

The compound 2(2-chloro-4-fluorophenoxy) ethanol-1 may be represented bythe formula and the compound 4(2-chloro-4-fiuorophenoxy) butanol-l maybe represented by the formula In accordance with the invention, it hasbeen found that by procedure involving reacting a metallic chlorofiuorophenate and ethylene chlorohydrin under-certain conditions, the newproduct 2(2-chloro-4fluorophenoxy) ethanol-1 may be made in good yields.The :following illustrates manufacture of such product by the indicatedreaction.

Example A.2-chloro-4-fiuorophenol (43 gms.0.34-

mol) was added to a solution of sodium (6.0 gms.--O.33 mol) in absolutemethanol. The mixture was heated at temperature of about 65 C. for about30 minutes. Ethylene chlorohydn'n, C H OCI, (24.5 gms.0.3 mol) was addeddropwise, and the resulting mass was heated at tem- .perature of about65 C. under refluxing conditions for 16'hours. A precipitate formedduring the reaction. At the end of the heating period, the precipitatewas filtered out and determined to be sodium chloride. was thendistilled, and there were recovered unreacted chlorohydrin, unreacted2-chloro-4-fiuorophenol, and 20 gms. of a product condensate boiling at160 C. at 18 mm. mercury pressure, at 165 .C..at .25 mm. pressure. Theproduct is a colorless liquid, sparingly soluble in Water but soluble inorganic hydrocarbon solvents. Chlorine content was 18.5% (weight) byanalysis, as compared with 18.7% theoretical. The product is alight-yellow, sweet-smelling oil having the sweet odor characteristic ofethers, and none of the strong phenolic odor. The product forms esterswith acids with evolution of about the theoretical quantity of water,thus showing the presence of a hydroxyl group.

Another run carried out under substantially the same conditions exceptethylene chlorohydrin and the sodium phenate were employed in about a2:1 molar proportion gave a yield of 87.5% of theory of the finalproduct.

In accordance with the invention, it has been found that4(2-chloro-4-fluorophenoxy) butanol-l may be made by reducing4(Z-chloroA-fluorophenoxy)-butanoic acid to the corresponding butanol,for example by reacting the butanoic acid with a metal hydride.4(2-chloro-4-fiuoro- The filtrate.

phenoxy)-butanoic acid may be prepared by procedure involving reactionof metallic phenoxides with butyrolactone. Thus, sodium2-chloro-4-fluoro-phenate is reacted with butyrolactone to form thesodium salt of 4(2- chloro-4-fiuorophenoxy)-butanoic acid, which salt isthen acidified to the free acid, as illustrated by the followingexample.

Example B.105 parts of 2-chloro-4-fiuorophenol were added to a solutionof 16.5 parts of sodium metal in about 157.8 parts of absolute ethanol,maintained in a 7 reaction vessel provided with a reflux condenser and astirrer. After stirring for a brief period, 61.7 parts of butyrolactonewere added, and the mixture was refluxed at about 80 C. -for 24 hours.The ethanol was then distilled out of the reaction mixture by heatingthe mixture to about 100 C. The residue was dissolved infwater andacidified with hydrochloric acid, thereby precipitating a. brownamorphous, cry stalline solid. The crystalline solid was dissolved inbenzene, treated with activated carbon and finally precipitated withpetroleum ether as white crystals. After filtering off the whitecrystals and drying at about 40 C., 57 parts of material identified as4(2chloro-4-fiuorophenoxy)sbutanoic acid were obtained.

Yield was 34% of theory. This compound is sparingly soluble in water andorganic hydrocarbon solvents, melts at 92-95" C. and had a neutralequivalent of 2295 as compared with 232.5 of theory. This compound isfurther described and claimed in our copending application Serial No.748,787, filed of even date and now US. Pat. No. 3,005,695.

The following example illustrates production of' thechlor'ofluorophenoxy butanol of the invent-ion by reduction of thebu-tanoic acid.

Example C.-23 gms. (0.1 mol) of 4(2-chloro-4-fluorophenoxy)-butanoicacid, prepared as detailed in Example B, were slurried in 200 ml. ofanhydrous'ethyl ether. This slurry was then added slowly to an etherealslurry of 5 gms.'(0.l3 mol) lithium aluminum hydride with cooling at 0to 5 C(over a period of about 30 minutes.

After'addition, the mixture was refluxed for about anhour at 35 C.following which the reaction mixture was diluted with water andacidified with aqueous sulfuric acid.. The ether layer was then driedover anhydrous sodium sulfate, and the ether was removed by distillationto recover 20 gms. of reaction product as a viscous oil remaining in thestill; Analysis of this crude product showed 14.2% chlorine, as comparedwith theory of 16.3%. Infrared analysis shows the absence of carboxylgroup indicating that no starting material remained, and shows thepresence of an ether linkage, a benzene ring, and a hydroxyl group alldemonstrating formation of the butanol. Yield was about 95% of theory.Vacu Theo. Found Fluorine 5. 1 5. 5' Carbon 54.9 55.2 Hydro en 4.3 4.4

thus establishing that the material reacted with the 4-cblorophenylisocyanate was 4(2-chloro-4-fluorophenoxy) butanol-l.

is As indicated, the invention also includes any ester of the above.chlorofiuorophenoxy ethanol and butanol. More particularly desirable arethe mono esters of the ethanol and butanol, especially of the ethanol.The alkali metal sulfates, particularly of the ethanol, have been foundto be notably effective.

The sulfates may be represented by the formula in which M may be analkali metal such as sodium or potassium, an alkaline earth, metal suchas calcium or barium, and the ammonium and organic amine salts such astriethanol amine or triethylamine.

It has been found, in accordance with the invention, that alkali metal2(2-chloro-4-fiuorophenoxy) ethyl sulfate may be made by reacting theabove described chlorofluorophenoxy ethanol with chlorosulfonic acid,reactions proceeding in accordance. with neutralized with aqueous sodiumhydroxide to effect reaction (B). Theresulting water solution was thenevaporated to recover a solid product, which was purified by washingwith acetone and drying, and identified as sodium2(2-chloro-4-fluorophenoxy) ethyl sulfate. The 22 gms. of productrecovered corresponded to a yield of 75% of theory.

Example E.-The trichloroacetic acid ester of the chlorofluorophenoxyethanol, represented by the following formula, may be made as follows:

About 25 g. (0.13 mol) of the above ethanol, 23 g. (0.14 ml.) oftrichloroacetic acid and about 150 ml. of toluene were placed in a3-necked, stirred reaction flask, and refluxed at about 110 C. for 6.5hrs., during which time 2.2 ml. water were collected in a Dean-Starkapparatus. For production of the. trichloroacetic acid ester, theoryWater recovery is 23ml. The reaction mixture was then distilled at pottemperature of about 170 C. and 36 gms, 82% of theory, of a liquidboiling at 151-158" C. at 3 mm. of Hg pressure were recovered ascondensate and identified as the trichloroacetic acid ester. Thismaterial is a light yellow liquid, insoluble in Water but soluble inorganic solvents such as acetone and xylene.

Example F.The 2,2-dichloropropionic acid ester of the ethanol,represented by the following formula, may be made as follows:

0 ll P01120520 o 0 (3120113 'represented by the following formula, maybe made as About 17 grns. (0.09 mol) of the ethanol product of Example Awere dissolved in 150 ml. of benzenee containing about 7.9 gms. (0.1mol) of pyridine. The solution was cooled to 23 C. and 13 gms. (0.09mol) of benzoyl chloride were added with stirring at below 5 C. Themixture was allowed to come to room temperature, was stirred for 3hours, and then allowed to stand overnight at room temperature, Thesolid pyridinium chloride was removed by filtration. The solvent wasthen removed by distillation. The residue product is semisolid at thispoint. Purification of the product was effected by dissolving in benzeneand drowning in hexane. On filtration, 22 gms. (84% of theory) of alight tan solid, having a melting point of 58-62 C. was recovered. Thismaterial is water insoluble, soluble in organic solvents such as acetoneand xylene, and of the following characteristics:

Theo. Found Saponification number 190 185 Carbon G1. 2 61. 5 Hydro en 4.1 4. 3

Example H.The phosphite ester of the ethanol, represented by thefollowing formula, may be made as follows:

After stirring for 3 hrs. at room temperature, the pyridinium chloridewas filtered off. The solvent was re moved in vacuo, and then thereaction mixture was heated to 150 C. at 4 mm. Hg pressure to remove asmall quantity of unreacted starting material. 12.5 gms. (79% of theory)of viscous liquid material, identified as the above phosphite ester,were recovered as pot residue. This material is water insoluble, andsoluble in organic solvents such as acetone, ether and xylene.

Example J.-The acetic ester of the butanol, represented by the followingformula, may be made as follows:

Procedure involves two steps represented by Tetrahydroiuran OHgCOClCl(CH2)4OCOCH n.

CH3C1FOK CI(CH)40C0CH3 CH3C1FO(CH;)4OCOOH3 K01 Step I was carried out inaccordance with known art, I. Am. Chem. Soc. 61, 2667 (1939), and stepII was carried out as follows:

2-chloro-4-fiuorophenol (50 gms. -0.34 mol), potassium hydroxide (19.1gms. -0.34 mol) and 200 ml. of xylene were refluxed with stirring andazetropic removal of 6.5 ml. of water to form the anhydrous potassiumphenate. Then, 54 gms. (0.36 mol) 4-chlorobutyl acetate were added withstirring at 120 C. Refluxing at 145 C. was continued for nearly 7 hours.The mass was cooled to room temperature, the potassium chloride filteredout, and the xylene filtrate was washed with 5% aqueous HCl. Removal ofxylene by distillation left 73.3 gms. of residual oil. Vacuumdistillation of the latter gave 45.8 gms. (51.7% of theory) of a yellowoil boiling at 132135 C. at 0.6 mm. Hg pressure. Infra-red analysisshowed the presence of an ether linkage and a carbonyl group.Saponification number for the acetate of 4(2-chloro-4-fluorophenoxy)-butanol is 215 theory; found 216.

Saponification of the foregoing yellow oil product resulted in formationof 4(2-chloro 4 fluoro-phenoxy)- butanol and CH COOK. Procedure was asfollows:

130.0 gms. (0.5 mol) of the yellow oil (the acetate) and 44.8 gms. (0.8mol) of potassium hydroxide in 95% ethanol (about 550 ml.) were refluxedfor 2.5 hrs. The mixture was then drowned in 1200 ml. of water and etherextracted. The ether was removed by distillation, giving 125 gms.residue. Vacuum distillation gave 101 gms. (92.3% yield) of colorlessoil boiling in the range of 141148 C. at pressure in the range of1.5-2.5 mm. of Hg, and infrared spectrographic analysis showed thepresence of a hydroxyl group, an ether linkage, a benzene ring andabsence of a carbonyl group, i.e. the 4(2-chloro-4-fluorophenoxy)-butanol product of Example C.

Example K.The benzoic ester of the butanol, represented by the followingformula, may be made as follows:

0 O(CH2)40([C5H5 The above procedure used in Example I for preparationof the acetate was followed substantially the same to make the benzoate.The first step involved reaction of benzoyl chloride withtetrahydrofuran using ZnClg catalyst. The second step comprised reactionof 4-chlorobutyl benzoate with potassium 2-chloro-4-fluoro-phenate asbefore. Evaporation of the xylene gave 121.7 gms. of crude residual.

oil. Vacuum distillation of the latter resulted in recovery of 64 gms.(59.3% of theory) of a viscous slightly yellow or dicotyledonousvarieties of plants such as smartweed,'

rape, lambs-quarters, bindweed, horsenettle and Canada "thistle, whichcommonly grow wild in agricultural and other soils, and also control themore pernicious mono cotyledonous plants or grasses such as ryegrass,foxtail, crabgrass and nutgrass.

The herbicides of the invention may be applied directly to the locus tobe treated. However, for reasons of economy and uniformity ofapplication, it is preferred to incorporate the active ingredient inliquid or solid diluents, and apply the active ingredient as a solutionina solvent or as a dispersion in a dispersing medium. The liquiddiluent may be a solvent for the active ingredient or the activeingredient may be dispersed in the liquid diluent. Known solvents,diluents, emulsifiers, carriers, etc. may be employed as customarily inthis art; 'For example, the ethyl sulfate is soluble in water and may beformulated as concentrated or dilute solutions in water. The ethanol andbutanol, being sparingly soluble in water'but soluble in organichydrocarbon solvents, may be formulated as emulsifiable concentrates anddilute solutions in organic hydrocarbon solvents such as fuel oils,petroleum naphthas, etc. The solutions or dispersions may contain theactive ingredient in an amount not less than /2 015a pound per gallonsof dispersion or solution, the more usual concentrations being in therange of 1 to 2 pounds per 100 gallons of dispersion or solution. Theactive ingredients may be impregnated on a suitable solid diluent.Typical diluents, which may be in finely divided or granular form,include diatomaceous earth, wood flours and silica gels. The dusts maycontain as little as about 0.5% by weight of active ingredients. Variousconventional ,wetting, dispersing and emulsifying agents may be added tothe herbicidal formulations of the type described in order to enhancethe wetting effect and produce improved dispersion of the activeingredient on the vegetation to which it is applied. Any of the knowntypes of spraying or dusting apparatus may be employed for applying theherbicide to the soil or vegetation to be treated, a primaryconsideration being uniformity of application.

The herbicides of the present invention are applied to the area to betreated in amount (pounds per acre) sufficient to afford the degree ofcontrol of vegetation desired in the given area. The optimum intensityof application of the desired herbicide will depend on such factors asamount of vegetation in the area, degree of permanency of planteradication desired, type of plants growing in the area, and climaticconditions. Hence, as is well known to those skilled in the art, therate of application actually used will depend largely on prevailinglocal conditions. In most instances, effective control of germinatingweed seeds and small weed seedlings may be realized by applying theherbicide at an over-all rate greater than about 1 pound per acre. Whereprolonged nonselective control of established vegetation is desired,dosages greater than about 4 pounds per acre may be employed.

Example 1.The following illustrates the herbicidal activity of thesodium 2(2-chloro-4-fluorophenoxy) ethyl The sulfate; of the invention;Data noted were the results of pre-emergence greenhouse tests carriedout by the macro screening technique as described by Shaw and Swanson(Weeds, vol. I, No; 4, p. 352, July 1952). Compound A was the sodium2(2-chloro-4-fiuorophenoxy) ethyl sulfate of the invention, and CompoundB was sodium 2(2,4-dichlorophenoxy) ethyl sulfate, a commercialherbicide. Quantities of active ingredients'used were 4 and 8 pounds peracre made up to 40 gal. water solutions per acre for spraying purposes.Test plot crops were corn and soybeans, and ryegrass was considered asrepresentative of grassy weeds, and rape representative of broad-leafweeds.

IliiInjury Rating; =none, 13=slight, 46=moderate, 79=sever'e I IR=Height Reduction.

K=Kill.

Untreated checks all figures zero.

It isnoted that Compound A of the invention is considerably more activeon both types of weeds than the corresponding 2,4-dichloro Compound B, acommercial herbicide. Compound A is only minimally injurious to corn,and less injurious to soybeans than Compound B. Accordingly, Compound Aafiords weed controlin corn and soybeans superior to that of Compound B.

Example 2.-The following illustrates the herbicidal activity of the2(2-chloro-4-fluorophenoxy) ethanol-1 and the 4(2-chloro-4-luorophenoxy)butanol-l compounds of the invention. Data noted are the results ofgreenhouse pre-emergence tests substantially the same as those ofExample 1. Compound'C was the'2(2-chloro-4-fiuorophenoxy) ethanol-1 ofthe invention; Compound D was the 4(2-chloro-4iuorophenoxy) butanol-l ofthe invention; Compound E was 4(2-dichlorophenoxy) butanol-l, andCompound F was the dimethylamine salt of 4(2,4-dichlorophenoxy)-butanoic acid, a commercial'herbicide. Quantities ofactive ingredients used were 2 pounds per acre made up for sprayingpurposes to 40 gal. acetone solutions per acre in the case of CompoundsC and D, and made up to 40 gal. water solution per acre in the case ofCompound F quantity of which was based on 100% active ingredientexpressed as the free acid. Compound E was used at strength of 16 poundsper acre made up for spraying purposes to 40 gal. acetone solution peracre. Ryegrass is considered representative of grassy weeds and rape asrepresentative of broad-leaf Weeds.

Percent plants killed or absent compared to untreated check plots 7These data demonstrate that under the pro-emergence test conditionsindicated the chloro-fiuoro ethanol and butanol compounds of theinvention are remarkably active with respect to hoth types of Weeds ascompared with (a) 4(2,4-dichlorophenoxy) ibutanol-l which has lowherbicidal activity with respect to either type of weed even whenapplied in an eight times greater dosage strength, and (b) thecommercial herbicide, the dimethylamine salt of 4(2,4-dichlorophenoxy)butyric acid, which compound has low activity as to broad-leaf andsubstantially no activity as to grassy type weeds.

Example 3.The following illustrates herbicidal activity of othercompounds of the invention. Data noted are the results of greenhousepre-emergence tests similar to those of Example 1. Compound L was thetrichloroacetic acid ester of the 2(2-chloro-4-fiuorophenoxy) ethanol-1,i.e. the product of Example E; Compound M was the 2,2- dichloropropionicacid ester of the ethanol, i.e., the prodnot of Example F; Compound Nwas the benzoic acid ester of the ethanol, i.e., the product of ExampleG; and Compound P was the phosphite ester of the ethanol, i.e., productof Example H. The 2,4-D was the dimethylamine salt of2,4-dichlorophen-oxyacetic acid, a commercial herlbicide. Quantities ofactive ingredients used were, except for Compound P, 4 pounds per acremade up for spraying purposes to 40 gal. acetone solution per acre, andin the case of Compound P dosage was at the rate of 16 pounds per acre.Ryegrass is considered representative of grassy weeds and rape asrepresentative of broad-leaf Weeds.

Percent weeds killed or absent compared with untreated check plots Broadleaf Grassy Weeds Weeds 99 85 65 S5 99 85 10 0 cre 0 0 Untreated check 00 We claim:

1. A compound selected from the group consisting of 2(2 chloro 4fiuorophenoxy) ethanol-1,4(2-chloro-4- fluorophenoxy) butanol-l, andesters thereof selected from the group consisting of their acetic acidesters; their trichloroacetic acid esters; their dichloropropionic acidesters; their benzoic acid esters; their alkali metal monosulfates, andtheir triesters of phosphorous acid.

2. The compound 2(2 -chloro-4-fiuorophenoxy) ethanol-l.

3. The compound sodium 2(2-chloro-4-fiuorophenoxy) ethyl sulfate.

4. The-compound 4(2-chloro-4-fluorophenoxy) buta- 1101-1.

5. The benzoic acid ester of 2(2-chloro-4-fluorophenoxy) ethanol-1.

6. The acetic acid ester of 4(2-chloro-4-fluorophenoxy) butanol-l.

References Cited by the Examiner UNITED STATES PATENTS 2,133,972 10/38Coleman et al 167-24 2,140,824 12/38 Vernon 260613 2,158,957 5/39Coleman et al 260- 613 2,573,769 11/51 Lambrech 712.6

(fitlier references on following page) 9 UNITED STATES PATENTS Lambrech260-613 X Chiddix et a1. 260-613 Mussell 71-23 Merrill 260-613 X Bnustet a1. 260-613 Harris et a1. 260-461 10 2,852,548 9/58 Gundel et' a1.260-458 2,902,518 9/59 Hurdis et a1. 260-613 2,904,421 9/ 59 Seaton71-23 5 CHARLES B. PARKER, Primary Examiner.

LEON ZI'TVER, IRVING MARCUS, JOSEPH P.

BRUST, Examiners.

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF2(2-CHLORO-4-FLUOROPHENOXY) ETHANOL-1,4(2-CHLORO-4FLUOROPHENOXY)BUTANOL-1, AND ESTERS THEREOF SELECTED FROM THE GROUP CONSISTING OFTHEIR ACETIC ACID ESTERS; THEIR TRICHLOROACETIC ACID ESTERS; THEIRDICHLOROPROPIONIC ACID ESTERS; THEIR BENZOIC ACID ESTERS; THEIR ALKALIMETAL MONOSULFATES, AND THEIR TRIESTERS OF PHOSPHOROUS ACID.